Developmental trajectories of cerebrovascular reactivity in healthy children and young adults assessed with magnetic resonance imaging

Abstract

Key pointsr Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels. r Normal development in children is associated with significant changes in blood pressure, cerebral blood flow (CBF) and cerebral oxygen metabolism. Therefore, it stands to reason that CVR will also undergo changes during this period.r The study acquired magnetic resonance imaging measures of CVR and CBF in healthy children and young adults to trace their changes with age.r We found that CVR changes in two phases, increasing with age until the mid-teens, followed by a decrease. Baseline CBF declined steadily with age.r We conclude that CVR varies with age during childhood, which prompts future CVR studies involving children to take into account the effect of development.Abstract Cerebrovascular reactivity (CVR) reflects the vasculature's ability to accommodate changes in blood flow demand thereby serving as a critical imaging tool for mapping vascular reserve. Normal development is associated with extensive physiological changes in blood pressure, cerebral blood flow and cerebral metabolic rate of oxygen, all of which can affect CVR. Moreover, the evolution of these physiological parameters is most prominent during childhood. Therefore, the aim of this study was to use non-invasive magnetic resonance imaging (MRI) to characterize the developmental trajectories of CVR in healthy children and young adults, and relate them to changes in cerebral blood flow (CBF). Thirty-four healthy subjects (17 males, 17 females; age 9-30 years) underwent CVR assessment using blood oxygen level-dependent MRI in combination with a computer controlled CO 2 stimulus. In addition, baseline CBF was measured with a pulsed arterial spin labelling sequence. CVR exhibited a gradual increase with age in both grey and white matter up to 14.7 years. After this break point, a negative correlation with age was detected. Baseline CBF maintained a consistent negative linear correlation across the entire age range. The significant age-dependent changes in CVR and CBF demonstrate the evolution of cerebral haemodynamics in children and should be taken into consideration. The shift in developmental trajectory of CVR from increasing to decreasing suggests that physiological factors beyond baseline CBF also influence CVR.

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

“…However, the combination of low vascular response and signal to noise ratio in the white matter could result in negative CVR values in some voxels. In the literature, healthy young adults are not expected to present with negative CVR values during a CO 2 challenge (Leung et al, 2016), except for in the ventricles and other areas occupied by cerebrospinal fluid (Blockley et al, 2011;Ravi et al, 2016). This has been the case in our own work as well (Chen and Pike, 2010b;Halani et al, 2015).…”

Cerebrovascular and ventilatory responses to acute normobaric hypoxia in girls and women

“…Cerebral perfusion is known to be developmentally mediated, and peaks between the ages of 5-10 years (Leung et al 2016). Consequently, these elevations in resting CBF have been linked to a reduced cerebrovascular reserve in response to hypercapnia (Leung et al 2016), though little is known about the response to hypoxia.…”

“…Cerebral perfusion is known to be developmentally mediated, and peaks between the ages of 5-10 years (Leung et al 2016). Consequently, these elevations in resting CBF have been linked to a reduced cerebrovascular reserve in response to hypercapnia (Leung et al 2016), though little is known about the response to hypoxia. Under hypobaric hypoxic conditions, an increase in anterior CBF has been observed (indexed by middle and anterior cerebral blood velocity; Gavlak et al 2013).…”

“…Cerebral perfusion shows distinct developmental patterns, peaking between the ages of 5-10 years, with values 30-50% greater than in adults, and a higher cerebral blood flow in girls compared to boys (Leung et al 2016). This greater perfusion in children is reflected in a reduced cerebrovascular reserve, as indicated by an attenuated cerebrovascular vasodilation to hypercapnia (Leung et al 2016). There is very limited data on the cerebrovascular response to hypoxia in the child, with one study demonstrating an increase in perfusion in the anterior cerebral circulation (indexed by increased middle and anterior cerebral artery blood velocity), but not in the posterior cerebral circulation (indexed by the basilar and posterior cerebral arteries) in children aged 6-13 years who completed a 5-day ascent to 3500 m (Gavlak et al 2013).…”

Reduced cerebrovascular reactivity among adolescents with bipolar disorder

“…10,11 Several studies have yielded similar findings in youth specifically. 9,12 Various youth studies have examined CVR using fMRI, finding impaired CVR in cerebral vasculopathy, 15 infarct areas in childhood stroke, 16 and sickle cell disease, 17 Studies of healthy participants have found gradual increases in CVR up to age 14.7 and thereafter, a negative correlation with age (age 9-30), 18 and lower signal-to-noise ratio in healthy young children compared to healthy young adults. 19 Additionally, our previous study examined regional differences, sex differences, and three modeling techniques for analyzing CVR in a healthy youth sample.…”